5,6-Dihydro-5-oxo-1,4-dithiino (2,3-d) pyridazine-2,3-dicarbonitriles

ABSTRACT

Novel compounds corresponding to the formula ##STR1## wherein R is H or an alkyl group having from 1 to about 7 carbon atoms. Their method of use in the control and kill of bacteria and fungi, and compositions containing the compounds as active ingredients are claimed.

SUMMARY OF THE INVENTION

The novel compounds of the present invention, hereinafter alternativelyreferred to as active compounds, correspond to the formula ##STR2##wherein R is either H or an alkyl group having from 1 to about 7 carbonatoms. Examples of suitable alkyl groups are methyl, ethyl, n-propyl,isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl andn-hexyl.

The active compounds, directly or as active ingredients in formulationsand compositions, exhibit, in antimicrobially-effective amounts,antimicrobial activity against fungi and bacteria. Hereinafter the terms"antimicrobial" and "antimicrobially-effective", when used inconjunction with the active compounds, will be employed to identifytheir activity against fungi and/or bacteria.

The active compounds are prepared by adding a corresponding4,5-dihalo-3-pyridiazone to disodiumdimercaptomaleonitrile indimethylformamide (DMF) as exemplified by the following equation:##STR3## wherein R is as defined hereinbefore, and R' is a halogenselected from Br or Cl.

The reaction mixture is stirred from about 10° C. to about 50° C. untilsubstantial completion of the reaction, usually from about 0.25 to about1 hour. Upon completion of the reaction, the mixture is poured intowater and allowed to stand for at least about 4 hours, during which timea solid product will precipitate. The solid is recovered by filtration,washed and dried. The compound can be used as prepared, however ifdesired it can be further purified by conventional techniques known toone skilled in the art.

Either of the starting materials can be used in excess of thestoichiometric requirements. However, ordinarily substantially equimolarproportions are employed.

The active compounds are slightly soluble in acetone and chloroform andare insoluble in water.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The following examples illustrate the present invention and the mannerby which it can be practiced but as such should not be construed aslimitations upon the overall scope of the same.

EXAMPLE 1 - Preparation of5,6-Dihydro-5-oxo-1,4-dithiino(2,3-d)-pyridazine-2,3-dicarbonitrile(Compound 1)

To a stirred solution of 20 g (0.1 mole) disodiumdimercaptomaleonitrilein 250 ml of DMF was added 16.5 g (0.1 mole) of4,5-dichloro-3-pyridiazone. The reaction mixture was stirred at roomtemperature (approximately 20° C.) for 0.25 hours and was thereafterpoured with stirring into 1.5 liters of water. The resulting mixture wasallowed to stand for four hours during which time a brown precipitateslowly formed. This precipitate was separated by filtration, washed withwater, and dried in vacuo to yield 10.2 g (43% yield from thepyridiazone) of a brown solid, m.p. (decomposition) 240°-260° C.

A sample was subjected to elemental analysis. The results obtained wereas follows:

    ______________________________________                                        Analysis for C.sub.8 H.sub.2 N.sub.4 OS.sub.2 :                               ______________________________________                                        Calcd.:    C, 41.01; H, 0.86;  N, 23.92.                                      Found:     C, 41.30; H, 1.11;  N, 23.69.                                      ______________________________________                                    

Infra-red spectrophotometry confirmed the assigned structure.

EXAMPLE 2 - Preparation of5,6-Dihydro-6-methyl-5-oxo-1,4-dithino(2,3-d)-pyridazine-2,3-dicarbonitrile(Compound 2)

To a stirred solution of 10.2 g (0.05 moles) ofdisodiumdimercaptomaleonitrile and 250 ml of DMF was added 9 g (0.05moles) of 4,5-dichloro-2-methyl-3(2-H)-pyridiazone. The reaction mixturewas stirred for 1 hour at approximately 50° C. and then poured withstirring into 1.5 liters of water. The resulting mixture was allowed tostand for 63 hours during which time a red brown precipitate slowlyformed. The precipitate was separated by filtration, washed with water,and dried in vacuo to yield 4.6 g (37% yield) of a red brown solid, m.p.175.7° C.

A sample was subjected to elemental analysis. The results obtained wereas follows:

    ______________________________________                                        Analysis for C.sub.9 H.sub.4 N.sub.4 OS.sub.2 :                               ______________________________________                                        Calcd.:    C, 43.54; H, 1.62;  N, 22.57.                                      Found:     C, 43.40; H, 1.88;  N, 22.38.                                      ______________________________________                                    

Infra-red spectrophotometry confirmed the assigned structure.

Following the same procedures as set forth in Examples 1 and 2 othercompounds of the present invention, wherein the substituent R representsstraight chain or branched chain moieties having from two to sevencarbon atoms, can readily be prepared fromdisodiumdimercaptomaleonitrile and the appropriate4,5-dihalo-2-alkyl-3(2-H)pyridiazone.

The active compounds of the invention are suitable for use asantimicrobials for the control of bacteria and fungi. This is not tosuggest that the active compounds and mixtures thereof with usualadditives are equally effective against all such organisms at the sameconcentration. The active compounds can be employed in an unmodifiedform or dispersed on a finely divided solid and employed as a dust. Suchmixtures can also be dispersed in water with the aid of a surface-activeagent and the resulting emulsion employed as a spray. In otherprocedures, the active compounds can be employed as the activeconstituents in solvent solutions, oil-in-water or water-in-oilemulsions. The augmented compositions are adapted to be formulated asconcentrates and subsequently diluted with additional liquid or solidadjuvants to produce the ultimate treating compositions. Good controland kill have been realized with compositions whereinantimicrobially-effective amounts of from about 1 to about 500 parts byweight of one or more of the active compounds per million parts of suchcompositions are employed. As stated hereinbefore the activeantimicrobially-effective amount to be employed against a given organismor in a certain composition can be determined by one skilled in the art.

Incorporation of the active compounds of this invention into materialswhich are subject to fungal attack inhibits the growth of the fungi andpreserves the original value of the materials. The active compounds aresufficiently nonvolatile and water-insoluble so that they will persiston or in such materials for long periods of time. Examples of materialswhich are adversely affected by fungal growth are latex and alkyl paintfilms, wood and wooden products. The active compounds are sufficientlyactive against fungi that only small quantities are required to preventmildew on paint films or wood rot. The active compounds are thereforeuseful for long-term protection against fungal growth in or on materialshaving a wood basis or a protective or decorative paint film or othercoating or covering subject to fungal attack.

In a standard activity test, samples of Compound 1 and Compound 2 wereindividually dispersed in warm melted nutrient agar which was pouredinto petri dishes and allowed to solidify, the active compounds beingemployed in an amount sufficient to provide from 1 to 500 parts byweight thereof per million parts (ppm) of the ultimate agar composition.The surface of the agar was inoculated with a variety of bacterial andfungal pest organisms, and the inoculated plates incubated underconditions conducive to bacterial and fungal growth. Similar checkplates in which the agar did not contain the active compounds or othertoxic compounds were similarly inoculated and incubated.

In these studies, Compounds 1 and 2 gave 100% growth inhibition (kill)and control of the following organisms, as set forth in the Table, atthe indicated concentrations in parts per million (ppm);

                  TABLE                                                           ______________________________________                                        Antimicrobial Activity                                                                     Concentration in ppm                                             Organism       Compound 1   Compound 2                                        ______________________________________                                        S. aureus      1            5                                                 S. typhosa     1            5                                                 A. niger       100          10                                                A. Fumigatus   50           10                                                C. pelliculosa 100          5                                                 C. albicans N  50           50                                                C. albicans D  50           50                                                B. subtilis    1            5                                                 A. aerogenes   10           100                                               P. aeruginosa  50           500                                               P. sp. strain 10                                                                             10           100                                               E. coli        5            10                                                S. marcesens   10           50                                                T. sp. med. col. VI                                                                          500          50                                                C. ips         100          10                                                Tri. sp. mad. P-42                                                                           50           50                                                T. mentagrophytes                                                                            50           5                                                 P. chrysogesum 100          50                                                ______________________________________                                    

What is claimed is:
 1. A compound of the formula ##STR4## wherein R iseither H or an alkyl group having from 1 to 7 carbon atoms.
 2. Thecompound of claim 1 which is5,6-Dihydro-5-oxo-1,4-dithiino(2,3-d)-pyridazine-2,-3-dicarbonitrile. 3.The compound of claim 1 which is5,6-Dihydro-6-methyl-5-oxo-1,4-dithiino(2,3-d)-pyridazine-2,3-dicarbonitrile.4. A method for controlling bacteria or fungi which comprises the stepof applying to bacteria and/or fungi or their habitat anantimicrobially-effective amount of a compound of the formula ##STR5##wherein R is H or an alkyl group having from 1 to about 7 carbon atoms.5. The method of claim 4 wherein R is H.
 6. The method of claim 4wherein R is CH₃.
 7. A composition for controlling bacteria or fungicomprising an antimicrobially-effective amount of a compound of theformula ##STR6## wherein R is either H or an alkyl group having from 1to 7 carbon atoms in combination with a solid or liquid diluent medium.8. The composition of claim 7 wherein R is H.
 9. The composition ofclaim 7 wherein R is CH₃.